Decreased SIRT3 in aged human mesenchymal stromal/stem cells increases cellular susceptibility to oxidative stress

Journal of Cellular and Molecular Medicine

Xue-Qing Wang²  Yong Shao²  Chong-Yi Ma²  Wei Chen²  Lu Sun²  Wei Liu¹  Dong-Yang Zhang²  Bi-Cheng Fu²  Kai-Yu Liu²  Zhi-Bo Jia²  Bao-Dong Xie²  Shu-Lin Jiang²  Ren-Ke Li³ 

[1] Key Laboratories of Myocardial Ischemia Mechanism and Treatment, Harbin Medical University, Ministry of Education, Harbin, China;Department of Cardiovascular Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China;Toronto General Research Institute, University Health Network and Department of Surgery, Division of Cardiac Surgery, University of Toronto, Toronto, ON, Canada

关键词: SIRT3;    oxidative stress;    ageing;    mesenchymal stromal/stem cells;    myocardium;    antioxidants;   

DOI  :  10.1111/jcmm.12395

来源: Wiley

【 摘 要 】

Abstract

Sirtuin3 (SIRT3) is an important member of the sirtuin family of protein deacetylases that is localized to mitochondria and linked to lifespan extension in organisms ranging from yeast to humans. As aged cells have less regenerative capacity and are more susceptible to oxidative stress, we investigated the effect of ageing on SIRT3 levels and its correlation with antioxidant enzyme activities. Here, we show that severe oxidative stress reduces SIRT3 levels in young human mesenchymal stromal/stem cells (hMSCs). Overexpression of SIRT3 improved hMSCs resistance to the detrimental effects of oxidative stress. By activating manganese superoxide dismutase (MnSOD) and catalase (CAT), SIRT3 protects hMSCs from apoptosis under stress. SIRT3 expression, levels of MnSOD and CAT, as well as cell survival showed little difference in old versus young hMSCs under normal growth conditions, whereas older cells had a significantly reduced capacity to withstand oxidative stress compared to their younger counterparts. Expression of the short 28 kD SIRT3 isoform was higher, while the long 44 kD isoform expression was lower in young myocardial tissues compared with older ones. These results suggest that the active short isoform of SIRT3 protects hMSCs from oxidative injury by increasing the expression and activity of antioxidant enzymes. The expression of this short isoform decreases in cardiac tissue during ageing, leading to a reduced capacity for the heart to withstand oxidative stress.

【 授权许可】

CC BY   
© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.